title: Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B.
abstract: We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4 (∼30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has the archetype pETBTY4 as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6')/aph(2″)], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producing S. aureus strains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses for aac(6')/aph(2″) and msrA using purified plasmid preparations. The ETB-producing S. aureus strains began to display high resistance to GM, which was parallel with the detection of aac(6')/aph(2″) and mecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however, msrA was hardly detected in ETB-producing S. aureus strains, and only five isolates were positive for both aac(6')/aph(2″) and msrA. In this study, we report the emergence of a fusion plasmid carrying the toxin gene etb and drug resistance genes. Prevalence of the pETBTY825 carrier may further increase the clinical threat, since ETB-producing S. aureus is closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.
authors.affiliation: Department of Bacteriology, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima City, Hiroshima, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Hisatsune
authors.forename: Hideki
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fudaba
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Oshima
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kato
authors.forename: Shizuo
authors.initials: S
authors.lastname: Kayama
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Sugai
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D003982:Dibekacin / Q000031:analogs & derivatives / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology; D005083:Exfoliatins / Q000096:biosynthesis / Q000235:genetics*; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D007169:Impetigo / Q000188:drug therapy / Q000382:microbiology; D007564:Japan; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids; D012189:Retrospective Studies; D013206:Staphylococcal Scalded Skin Syndrome / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D005083:Exfoliatins; D005839:Gentamicins; D003982:Dibekacin; D004917:Erythromycin; C031986:arbekacin